Epstein-Barr virus (EBV) is a gamma herpes virus that resides in approximately 85% of adults in the United States. EBV specifically infects human B cells, which in cell culture or in an immune compromised host, will transform to a malignant phenotype and grow without control (i.e., immortalize). Most people acquire EBV sub-clinically, but for some, the initial infection is heralded by infectious mononucleosis. Subsequently, a normal, healthy adult harbors few EBV+ B lymphocytes in the body (so called “latently infected”), and an “army” of EBV-specific T cells that keep the EBV+ B cells “in check” from ever reactivating and causing EBV+ B cell lymphoma in the human for the rest of their life. However, if an individual has suppression of their T lymphocytes, for whatever reason (e.g., congenital, acquired, or iatrogenic immune deficiency that follows solid organ transplantation), endogenous reactivation of the latently infected B cells by the lytic form of EBV can be fatal. Further, in immune suppressed children who have yet to be exposed to EBV, primary infection by the virus during states of iatrogenic immune deficiency such as occurs with immune suppressive therapy for solid organ transplantation is highly fatal. Indeed, 20% of children who undergo liver transplantation die from this complication (i.e., post-transplant lymphoproliferative disorder, or PTLD).
PTLD is highly fatal in children undergoing solid organ transplantation as noted above, and complicates approximately 2% of adult patients undergoing kidney transplantation and up to 20% of cardiac transplants in adults. These patients must take immunosuppressive therapy so they do not reject their transplanted organs. This therapy suppresses T cells that guard against either primary EBV infection or re-infection from latent EBV. PTLD is fatal in approximately 30–50% of cases. For the vast majority of adults, treatment of PTLD consists of reduction in immune suppressive therapy, sometimes followed by immunotherapy or chemotherapy. Reduction in immune therapy is an option in adult transplant patients because adults are previously exposed to EBV and therefore have immunologic memory T cells that can be activated against PTLD once immune suppression is reduced. However, the vast majority of children do not have EBV specific T cells, and in childhood solid organ transplants, the lack of a prior infection/exposure of EBV can lead to a rapid, often fatal complication from EBV-associated PTLD, as noted above. Indeed, some transplantation centers will not allow liver transplantation if a child does not have prior exposure to EBV.